Future antiviral polymers by plasma processing.

Coronavirus disease 2019 (COVID-19) is largely threatening global public health, social stability, and economy. Efforts of the scientific community are turning to this global crisis and should present future preventative measures. With recent trends in polymer science that use plasma to activate and enhance the functionalities of polymer surfaces by surface etching, surface grafting, coating and activation combined with recent advances in understanding polymer-virus interactions at the nanoscale, it is promising to employ advanced plasma processing for smart antiviral applications. This trend article highlights the innovative and emerging directions and approaches in plasma-based surface engineering to create antiviral polymers. After introducing the unique features of plasma processing of polymers, novel plasma strategies that can be applied to engineer polymers with antiviral properties are presented and critically evaluated. The challenges and future perspectives of exploiting the unique plasma-specific effects to engineer smart polymers with virus-capture, virus-detection, virus-repelling, and/or virus-inactivation functionalities for biomedical applications are analysed and discussed.

Relationship between serum quantitative HBsAg and HBV DNA levels in chronic hepatitis B patients.

Serum hepatitis B surface antigen (HBsAg) level has been developed as an important marker to predict treatment outcome recent years. The authors aimed to identify the correlation between quantitative HBsAg and hepatitis B virus (HBV) DNA level in chronic hepatitis B (CHB) patients and explore whether quantitative HBsAg can be used as a surrogate marker of serum HBV DNA for CHB patients. One hundred seventy-three patients were included in this study. Patients were divided into two groups: Hepatitis B e antigen (HBeAg) positive and negative patients. There was a positive correlation between quantitative HBsAg and HBV DNA level in HBeAg positive patients (r = 0.509, P < 0.001) and poor correlation in HBeAg negative patients (r = 0.176, P = 0.096). Interestingly, completely no correlation (r = -0.01, P = 0.994) was found in younger HBeAg negative patients (<40 years old), whereas in older HBeAg negative patients (>40 years old) there is a positive correlation (r = 0.448, P = 0.003). Mean HBsAg titer and Alanine aminotransferase (ALT) level were significantly higher in HBeAg positive group (3.81 log10 IU/mL; 105 IU/mL) than in negative group (2.85 log10  IU/mL; 32 IU/mL) (P <  0.001). We concluded that quantitative HBsAg could reflect HBV DNA level in HBeAg positive patients, but could not surrogate for HBV DNA level in HBeAg negative patients. Our study improves understanding of the relationship between HBsAg titers and HBV DNA levels in CHB patient and may have implications for future treatment algorithms evaluating the HBsAg titers in both HBeAg positive and negative patients.

Characteristics and risk factors for invasive fungal infection in hospitalized patients with acute-on-chronic hepatitis B liver failure: a retrospective cohort study from 2010 to 2023.

Background and aim: The global burden of invasive fungal infections (IFIs) is emerging in immunologic deficiency status from various disease. Patients with acute-on-chronic hepatitis B liver failure (ACHBLF) are prone to IFI and their conditions are commonly exacerbated by IFI. However, little is known about the characteristics and risk factors for IFI in hospitalized ACHBLF patients. Methods: A total of 243 hospitalized ACHBLF patients were retrospectively enrolled from January 2010 to July 2023. We performed restricted cubic spline analysis to determine the non-linear associations between independent variables and IFI. The risk factors for IFI were identified using logistic regression and the extreme gradient boosting (XGBoost) algorithm. The effect values of the risk factors were determined by the SHapley Additive exPlanations (SHAP) method. Results: There were 24 ACHBLF patients (9.84%) who developed IFI on average 17.5 (13.50, 23.00) days after admission. The serum creatinine level showed a non-linear association with the possibility of IFI. Multiple logistic regression revealed that length of hospitalization (OR = 1.05, 95% CI: 1.02-1.08, P = 0.002) and neutrophilic granulocyte percentage (OR = 1.04, 95% CI: 1.00-1.09, P = 0.042) were independent risk factors for IFI. The XGBoost algorithm showed that the use of antibiotics (SHAP value = 0.446), length of hospitalization (SHAP value = 0.406) and log (qHBV DNA) (SHAP value = 0.206) were the top three independent risk factors for IFI. Furthermore, interaction analysis revealed no multiplicative effects between the use of antibiotics and the use of glucocorticoids (P = 0.990). Conclusion: IFI is a rare complication that leads to high mortality in hospitalized ACHBLF patients, and a high neutrophilic granulocyte percentage and length of hospitalization are independent risk factors for the occurrence of IFI.

Quality Control in RT-PCR Viral Load Assays: Evaluation of Analytical Performance for HIV, HBV, and HCV.

Introduction: Quality Control Management (QCM) in clinical laboratories is crucial for ensuring reliable results in analytical measurements, with biological variation being a key factor. The study focuses on assessing the analytical performance of the Reverse Transcription Polymerase Chain Reaction (RT-PCR) system for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV). Five models proposed between 1999 and 2014 offer different approaches to evaluating analytical quality, with Model 2 based on biological variation and Model 5 considering the current state of the art. The study evaluates the RT-PCR system's analytical performance through Internal Quality Control (IQC) and External Quality Control (EQC). Materials and Methods: The Laboratório Central de Saúde Pública do Estado do Ceará (LACEN-CE) conducted daily IQC using commercial kits, and EQC was performed through proficiency testing rounds. Random error, systematic error, and total error were determined for each analyte. Results: Analytical performance, assessed through CV and random error, met specifications, with HIV and HBV classified as "desirable" and "optimal." EQC results indicated low systematic error, contributing to total errors considered clinically insignificant. Conclusion: The study highlights the challenge of defining analytical specifications without sufficient biological variability data. Model 5 is deemed the most suitable. The analytical performance of the RT-PCR system for HIV, HBV, and HCV at LACEN-CE demonstrated satisfactory, emphasizing the importance of continuous quality control in molecular biology methodologies.

The Connection between MiR-122 and Lymphocytes in Patients Receiving Treatment for Chronic Hepatitis B Virus Infection.

New molecular predictors for the response to treatment in HBV (hepatitis B virus) infection are assessed. Among them is miR-122. Our article searches the connection between miR-122 and the counts of lymphocytes in chronic HBV patients receiving treatment. We included the sera of 38 Romanian subjects with chronic HBV infection (20 receiving treatment and 18 not receiving treatment) and 5 healthy controls. The expression of miR-122 was determined using RT-PCR (real-time PCR) and a 2-ΔΔCT method. Two systematic analyses were also performed on databases (PUBMED, Web of Science, and Science Direct), eliminating systematic reviews, editorials, letters to editors, meta-analyses, reviews, conference proceedings, or pre-print manuscripts. We included human-based articles following the PRISMA criteria and the Newcastle Ottawa Assessment Scale for Case-Control and Cohort studies. R 4.2.2 was used for statistics, and MIENTURNET and STRING were used for the bioinformatic analysis. Our results showed a link between the variations in the expression of miR-122 and the counts of lymphocytes in HBV Romanian patients receiving therapy. Treatment influenced miR-122 and the lymphocyte numbers. This is the first study with these results, and it may lead to a new perspective on the inter-relationships between microRNAs and therapy in HBV patients.

Knowledge, Awareness and Prevalence of Hepatitis B Among Urban Slum Dwellers and Residents of Social Welfare Home: A Cross sectional Study From Eastern India.

Background/aims: In view of limited data on the knowledge and awareness of hepatitis B virus (HBV) and the available preventive strategies at the community level, it was aimed to analyse the knowledge and awareness of HBV in the community. Methods: A cross-sectional questionnaire-based survey was conducted among residents of an urban slum and a social welfare home in Bhubaneswar, Odisha, from October 2019 to April 2021. The prevalence of HBV infection was also measured by testing the serum positivity for hepatitis B surface antigen using rapid point-of-care test kits. The statistical analysis was done by using the software SPSS version 20. Results: A total of 370 individuals (mean age 38.7 ± 14.9 years, males: 55.1%) were assessed. Although 18.1% (67) had good knowledge, only 16.7% (62) had good awareness about HBV. Approximately 14.8% (55) knew that a vaccine is available in the country for HBV, and 6.2% (23) identified themselves as being vaccinated. Educational status was a significant independent predictor of knowledge and awareness such that people with education level of matriculation and above had odds of 11.05 (95% confidence interval: 5.3-22.7) and 14.7 (95% confidence interval: 6.5-33.1) for having good knowledge and awareness regarding HBV, respectively. A total of 10 participants tested positive for hepatitis B surface antigen contributing to a point prevalence rate of 2.7%. The proportion of individuals with an education status of matriculation and above was higher in the slum area when compared with the welfare home (67% vs 33%; P < 0.001), the knowledge (71.6% vs 28.4%; P < 0.001) and so was the awareness (71% vs 29%; P < 0.001) about HBV as well. Conclusion: The relatively low figures of knowledge and awareness identified in our study undermine the need for intensification of health education and promotion activities regarding the prevalence of hepatitis B infection on a large scale at the community level.

Barriers that prevent adults living with HBV infection from participating in clinical research: experience from South Africa.

High profile international goals have been set for the elimination of hepatitis B virus (HBV) infection as a public health threat by the year 2030. Developing and expanding equitable, accessible translational HBV research programmes that represent real-world populations are therefore an urgent priority for clinical and academic communities. We present experiences and insights by an expert interdisciplinary group focusing on barriers that impede adults living with HBV infection from participating in clinical studies. Our viewpoint describes barriers we have identified through working in a variety of settings across South Africa, including lack of education and awareness, experiences of stigma and discrimination, challenges for governance and data management, and a burden of complex morbidity. Through identifying these challenges, we propose solutions and interventions, highlight new approaches, and provide a framework for future research.

Health inequalities in the management of chronic hepatitis B virus infection in patients from sub-Saharan Africa in high-income countries.

Chronic hepatitis B virus disproportionately affects migrant communities in high-income countries, reflecting increased migration from sub-Saharan Africa. Chronic hepatitis B virus is endemic in sub-Saharan Africa, yet the natural history of chronic infection experienced by patients remains incompletely understood, with evidence of variability across genotypes and regions within sub-Saharan Africa. Clinical guidelines recommending treatment thresholds are not specific to sub-Saharan African patients and are based on natural history studies from Western Pacific Asian countries. Access to standard of care treatment is available for sub-Saharan African people with chronic hepatitis B virus infection in high-income countries; however, the evidence base for these treatments was not established in this cohort and areas of uncertainty remain, particularly regarding HCC surveillance and treatment discontinuation. Participation in phase III clinical trials for chronic hepatitis B therapies is almost non-existent amongst sub-Saharan African patients, even when residing in high-income countries that participate in multicentre trials. Engagement with sub-Saharan African patients with chronic hepatitis B in high-income countries is challenging because of the stigma associated with the diagnosis, absence of routine screening systems and the complexities involved in navigating the healthcare system. Nonetheless, improved engagement is critical if we are to achieve global hepatitis B virus elimination.

Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis.

Background & Aims: The risk of serious clinical outcomes following cessation of nucleos(t)ide analogues (NUCs) in individuals with chronic hepatitis B remains poorly characterized. This systematic review and meta-analysis aimed to evaluate current literature on this issue. Methods: We searched PubMed, Embase, and Web of Science for NUC stop studies that noted clinical outcomes published between January 1, 2006 and August 18, 2022. We performed meta-research analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with non-overlapping populations to provide risk estimates for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flare-related death or liver transplantation. Results: The meta-research analysis included 50 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only ten studies prespecified safety events as the study outcome, and only four had an outcome definition to include hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 15 studies with 4,525 individuals and estimated that severe hepatitis flares or decompensation would occur in 1.21% (95% CI 0.70-2.08%), with significant heterogeneity (I 2 = 54%, p <0.01), while hepatitis flare-related death or liver transplantation would occur in 0.37% (95% CI 0.20-0.67%), without significant heterogeneity (I 2 = 0.00%, p = 1.00). Conclusions: Current literature on the risk of serious clinical outcomes following NUC cessation is very limited and highly heterogeneous. Pooled analyses of available data found approximately 1% of patients who stopped NUCs developed severe flares or hepatic decompensation. Impact and implications: Current literature regarding the safety concerns surrounding NUC cessation for individuals with chronic hepatitis B is limited and heterogeneous in designs and characteristics, and thus should be interpreted with great caution. Based on currently available data, the proportion of patients that develop severe hepatitis flares or hepatic decompensation was estimated at 1.21% and that of flare-related death or liver transplantation at 0.37%. Our findings are important for individuals receiving nucleos(t)ide analogues for hepatitis B virus infection because we not only pooled currently available data to estimate the risk of serious clinical adverse events following treatment cessation but also uncovered critical limitations of existing literature regarding the safety of finite therapy.

Identification of selective hepatitis delta virus ribozyme inhibitors by high-throughput screening of small molecule libraries.

Background & Aims: Chronic hepatitis delta is the most severe form of chronic viral hepatitis and is associated with faster progression towards cirrhosis, liver decompensation, and hepatocellular carcinoma. Hepatitis delta virus (HDV)'s tight dependency on hepatitis B virus and the host cell machinery for its life cycle limits the development of direct-acting antivirals. Thus, we aimed to identify compounds that could block HDV replication by targeting its antigenomic ribozyme. Methods: We generated stable Huh7 human hepatoma cells expressing a reporter gene (Gaussia luciferase) either downstream (Gluc-2xRz) or upstream (2xRz-Gluc) of two HDV antigenomic ribozyme sequences. We performed high-throughput screening of three small molecule libraries. The secreted luciferase was measured as a readout of ribozyme inhibition upon addition of the molecules. Each plate was considered valid when the Z factor was >0.4. Specificity and toxicity evaluations were performed for the hits with a Z-score >5 and half-maximal inhibitory concentration was calculated by performing a dose-response experiment. Results: A dose-dependent induction of luciferase expression was detected in Gluc-2xRz-transfected cells incubated with the antisense morpholino, suggesting that the catalytic activity of the ribozyme cloned downstream of the reporter gene was efficiently inhibited. Among the 6,644 compounds screened, we identified four compounds that showed a specific inhibitory effect on the HDV antigenomic ribozyme in Gluc-2xRz cells, i.e. three histone deacetylase inhibitors and the purine analogue 8-azaguanine. The latter also significantly decreased HDV replication (by 40%) in differentiated HepaRG cells six days post infection. Conclusion: Using a novel cell culture model, we identified four small molecules active against the antigenomic HDV ribozyme. These results may provide insights into the structural requirements of molecules designed for the potent and specific inhibition of HDV replication. Impact and implications: Chronic hepatitis delta is the most severe form of chronic viral hepatitis and is associated with faster progression towards cirrhosis, liver decompensation, and the development of hepatocellular carcinoma. Despite the current development of several new compounds, there is still a need for efficient antiviral treatments specifically targeting hepatitis delta virus (HDV). This work describes a novel cell culture model that allows for the high-throughput screening of compounds able to inhibit HDV ribozymes. We identified four small molecules active against the antigenomic HDV ribozyme (the ribozyme involved in the early step of HDV replication), with the strongest activity shown by 8-azaguanine, a purine analogue. Our data may provide insights into the structural requirements of molecules designed to inhibit HDV.

ß-CATENIN stabilizes HIF2 through lncRNA and inhibits intravenous immunoglobulin immunotherapy.

Introduction: Tumor-initiating cells (TICs) are rare, stem-like, and highly malignant. Although intravenous hepatitis B and C immunoglobulins have been used for HBV and HCV neutralization in patients, their tumor-inhibitory effects have not yet been examined. Hepatitis B immunoglobulin (HBIG) therapy is employed to reduce hepatocellular carcinoma (HCC) recurrence in patients after living donor liver transplantations (LDLT). Hypothesis: We hypothesized that patient-derived intravenous immunoglobulin (IVIG) binding to HCC associated TICs will reduce self-renewal and cell viability driven by ß-CATENIN-downstream pathways. ß-CATENIN activity protected TICs from IVIG effects. Methods: The effects of HBIG and HCIG binding to TICs were evaluated for cell viability and self-renewal. Results: Inhibition of ß-CATENIN pathway(s) augmented TIC susceptibility to HBIG- and HCIG-immunotherapy. HBV X protein (HBx) upregulates both ß-CATENIN and NANOG expression. The co-expression of constitutively active ß-CATENIN with NANOG promotes self-renewal ability and tumor-initiating ability of hepatoblasts. HBIG bound to HBV+ cells led to growth inhibition in a TIC subset that expressed hepatitis B surface antigen. The HBx protein transformed cells through ß-CATENIN-inducible lncRNAs EGLN3-AS1 and lnc-ß-CatM. Co-expression of constitutively active ß-CATENIN with NANOG promoted self-renewal ability of TICs through EGLN3 induction. ß-CATENIN-induced lncRNAs stabilized HIF2 to maintain self-renewal of TICs. Targeting of EGLN3-AS1 resulted in destabilization of EZH2-dependent ß-CATENIN activity and synergized cell-killing of TICs by HBIG or HCIG immunotherapy. Discussion: Taken together, WNT and stemness pathways induced HIF2 of TICs via cooperating lncRNAs resulting in resistance to cancer immunotherapy. Therefore, therapeutic use of IVIG may suppress tumor recurrence through inhibition of TICs.

Psoas Muscle Index: A Simple and Reliable Method of Sarcopenia Assessment on Computed Tomography Scan in Chronic Liver Disease and its Impact on Mortality.

Objectives: Psoas muscle parameters have been proposed as a simple and quick method for sarcopenia assessment. The aim of this study was to assess sarcopenia in cirrhotics by psoas muscle on computed tomography and its impact on mortality. Methods: One hundred and fifty patients (75 cirrhotics, 75 subjects) were assessed for psoas muscle on CT scan. Psoas muscle index (PMI) was calculated as 'total psoas muscle area/(height of subject)2'. Cut off values for sarcopenia diagnosis were derived from local subjects (n = 75) who did not have cirrhosis/other causes of sarcopenia. Results: Sarcopenia assessed by PMI was seen in 36% (n = 27) of the cirrhotics. Sarcopenia was significantly higher in patients having Child-Pugh C. Ascites, hepatic encephalopathy (HE) and gastro-intestinal bleed were seen in 48%, 18.7% and 24%, respectively. Sarcopenia was significantly associated with ascites and HE (P < 0.05). Out of the 75 cases, 53 cases completed the follow-up period of 1 year. Among the 20 cases who had sarcopenia, 35% (n = 7) succumbed to liver-related illness during 1 year follow-up, and out of the 33 cases without sarcopenia, only 6% (n = 2) died. The association of sarcopenia and 1 year mortality was statistically significant (P = 0.01). Conclusions: The PMI, a simple method for sarcopenia assessment detected sarcopenia in 36% of cirrhotics. Patients with sarcopenia had a significantly higher 1 year mortality rate and appropriate prognostication of such patients is needed.

Recompensation in Cirrhosis: Current Evidence and Future Directions.

The natural history of cirrhosis has usually been conceptualized in the context of progression from compensated cirrhosis to subsequent stages of decompensation. While this unidirectional concept is the most common pathophysiological trajectory, there has been an emerging understanding of a subgroup of patients which undergo recompensation. While literature mostly based on transplant waitlist registries have indicated towards such a population who experience disease regression, the overall literature about this entity remains inexplicit. An effort to generate consensus on defining recompensation has been attempted which comes with its own nuances and limitations. We summarize the available literature on this emerging yet controversial concept of recompensation in cirrhosis and delve into future implications and impact on real-life practice.

Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells.

Background & Aims: Patterns of liver HBV antigen expression have been described but not quantified at single-cell resolution. We applied quantitative techniques to liver biopsies from individuals with chronic hepatitis B and evaluated sampling heterogeneity, effects of disease stage, and nucleos(t)ide (NUC) treatment, and correlations between liver and peripheral viral biomarkers. Methods: Hepatocytes positive for HBV core and HBsAg were quantified using a novel four-plex immunofluorescence assay and image analysis. Biopsies were analysed from HBeAg-positive (n = 39) and HBeAg-negative (n = 75) participants before and after NUC treatment. To evaluate sampling effects, duplicate biopsies collected at the same time point were compared. Serum or plasma samples were evaluated for levels of HBV DNA, HBsAg, hepatitis B core-related antigen (HBcrAg), and HBV RNA. Results: Diffusely distributed individual HBV core+ cells and foci of HBsAg+ cells were the most common staining patterns. Hepatocytes positive for both HBV core and HBsAg were rare. Paired biopsies revealed large local variation in HBV staining within participants, which was confirmed in a large liver resection. NUC treatment was associated with a >100-fold lower median frequency of HBV core+ cells in HBeAg-positive and HBeAg-negative participants, whereas reductions in HBsAg+ cells were not statistically significant. The frequency of HBV core+ hepatocytes was lower in HBeAg-negative participants than in HBeAg-positive participants at all time points evaluated. Total HBV+ hepatocyte burden correlated with HBcrAg, HBV DNA, and HBV RNA only in baseline HBeAg-positive samples. Conclusions: Reductions in HBV core+ hepatocytes were associated with HBeAg-negative status and NUC treatment. Variation in HBV positivity within individual livers was extensive. Correlations between the liver and the periphery were found only between biomarkers likely indicative of cccDNA (HBV core+ and HBcrAg, HBV DNA, and RNA). Impact and Implications: HBV infects liver hepatocyte cells, and its genome can exist in two forms that express different sets of viral proteins: a circular genome called cccDNA that can express all viral proteins, including the HBV core and HBsAg proteins, or a linear fragment that inserts into the host genome typically to express HBsAg, but not HBV core. We used new techniques to determine the percentage of hepatocytes expressing the HBV core and HBsAg proteins in a large set of liver biopsies. We find that abundance and patterns of expression differ across patient groups and even within a single liver and that NUC treatment greatly reduces the number of core-expressing hepatocytes.

Hepatitis B virus infection combined with nonalcoholic fatty liver disease: Interaction and prognosis.

Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.

Predicting the survival benefit of liver transplantation in HBV-related acute-on-chronic liver failure: an observational cohort study.

Background: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients. Methods: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT. Findings: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated. Interpretation: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT. Funding: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.

Background & Aims: The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Methods: Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. Results: The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. Conclusions: The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Impact and Implications: Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Unemployment and Illiteracy Are Predictors of Hepatitis B Virus-Related Stigma and Discrimination.

Background: HBV is a serious threat to society in India as around 1,00,000 people die from HBV every year. However, very few studies from India have evaluated the magnitude of stigma faced by HBV patients. So, there was an unmet need to estimate the HBV-related stigma to design the preventive strategies. Hence, the aim of this study was to quantitatively assess the proportions of stigma and discrimination and factors predicting them among HBV patients. Methods: A cross-sectional study was conducted from May 2016 to October 2019. A total of 350 HBV patients and 100 healthy respondents were interviewed for knowledge and awareness about HBV and various stigma characteristics. Results: The mean age of HBV subjects was 45.10 ± 11.70 years, and controls were 36.20 ± 12.27 years; males constituted 60% of HBV subjects and 71% of controls. Negative symptoms such as shame, avoidance, and putting others in danger were felt by 70-90% of HBV patients. Around 60% of HBV patients felt that hepatitis B could be transmitted by sharing utensils thinking that saliva is the mode of transmission. The knowledge about transmission of HBV by sexual intercourse, intravenous drug use, and mother to child was present in 88%, 75%, and 52% of HBV patients and 32%,38%, and 40% of healthy individuals, respectively. Multivariate logistic regression revealed that male gender (AOR-2.38, CI 1.48-3.81, P < 0.01), under matriculates (AOR-2.03, CI 1.22-3.44, P < 0.01) and unemployed (AOR-2.16, CI 1.33-3.53, P < 0.01) were significant independent predictors of significant discrimination. Conclusion: The magnitude of HBV-related stigma is high in the Indian population, and illiteracy and unemployment were significant predictors of a severe grade of discrimination associated with HBV.

METTL16 regulates m6A methylation on chronic hepatitis B associated gene HLA-DPB1 involved in liver fibrosis.

The role of genetic factors in the occurrence and progression of CHB (CHB) is still not fully explored. In recent years, genome-wide association studies on CHB patients have demonstrated that a large number of CHB-associated single nucleotide polymorphisms exist in the gene intron, which may regulate expression at the transcriptional level. Modification of RNA m6A methylation is one of the key mechanisms regulating gene expression. Here we show that METTL16, an m6A regulator involved in mRNA intron splicing, is differentially expressed in CHB the tissue of patients who has definite diagnosis of mild and severe fibrosis. At the same time, there are also significant differences in the expression of CHB-associated genes such as HLA-DPA1 and HLA-DPB1. The expression of HLA-DPB1 is related to METTL16. Furthermore, analyses of RNA binding of METTL16 and HLA-DPB1 show that the silencing of METTL16 in astrocytes downregulates m6A and expression of HLA-DPB1. In conclusion, METTL16 participates in the progression of CHB fibrosis by regulating the m6A level and expression of HLA-DPB1.